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Conditioned Placebo Dose Reduction: A New Treatment in Attention-Deficit Hyperactivity Disorder?

Sandler, Adrian D. MD*; Glesne, Corrine E. PhD*; Bodfish, James W. PhD†‡

Journal of Developmental & Behavioral Pediatrics: June 2010 - Volume 31 - Issue 5 - p 369-375
doi: 10.1097/DBP.0b013e3181e121ed
Original Article

Objective: This study examined if pairing a placebo with stimulant medication produces a placebo response that allows children with attention-deficit hyperactivity disorder (ADHD) to be maintained on a lower dose of stimulant medication. The primary aim was to determine the efficacy, side effects, and acceptability of a novel conditioned placebo dose reduction procedure.

Method: Participants included 99 children ages 6 to 12 years with ADHD. After an initial double-blind dose finding to identify optimal dose of mixed amphetamine salts, subjects were randomly assigned to 1 of 3 treatments of 8-week duration: (a) conditioned placebo dose reduction condition (50% reduced dose/placebo [RD/P]) or (b) a dose reduction only condition (RD) or (c) a no reduction condition (full dose). The innovative conditioned placebo dose reduction procedure involved daily pairing of mixed amphetamine salts dose with a visually distinctive placebo capsule administered in open label, with full disclosure of placebo use to subjects and parents.

Results: Seventy children completed the study. There were no differences in subject retention among the 3 groups. Most subjects in the RD/P group remained stable during the treatment phase, whereas most in the RD group deteriorated. There was no difference in control of ADHD symptoms between the RD/P group and the full dose group, and both RD/P and full dose groups showed better ADHD control than the RD group. Treatment emergent side effects were lowest in the RD/P group.

Conclusion: Pairing placebos with stimulant medication elicits a placebo response that allows children with ADHD to be effectively treated on 50% of their optimal stimulant dose.

From the *Olson Huff Center, Mission Children’s Hospital, Asheville, NC; Departments of †Psychiatry; ‡Pediatrics, Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Received January 2010; accepted April 2010.

The study was supported by the National Institute of Mental Health, Grant R21 MH068146.

Adrian Sandler and Corrine Glesne participated in the design and implementation of the study. Adrian Sandler had full access to all the data in the study and had the final responsibility for the decision to submit for publication. James Bodfish participated in the design of the study and data analysis.

The NIMH had no involvement in any aspects of the study or this paper.

Address for reprints: Adrian D. Sandler, MD, Olson Huff Center, 11 Vanderbilt Park Drive, Asheville NC 28803; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.